How Does Doxepin Work?

Unlike other antidepressants, Doxepin doesn’t act as a sedative to help you sleep.

Instead, it’s been shown to help control your circadian rhythm, the internal process that regulates your sleep-wake cycle. This is what tells you when it’s time to go to sleep each night and wake up each morning.

Histamine, a chemical produced throughout your body, plays a role in that regulation.

Think of histamine as part of your internal alarm clock. When histamine neurons are active, we feel bright, fresh, and awake. This is obviously helpful during the day, as it produces a well-rested, alert state.

It can drive you insane if it’s producing the same kind of productive, alert wakefulness at 3 AM, though.

Low doses of Doxepin bind to histamine H1 receptors in your brain and block them. This helps prevent histamine from shaking you awake in the middle of the night, telling you it’s time to start staring at the ceiling for a few hours.

Over the course of a 3-month clinical trial, a small dose of the drug helped participants with insomnia:

  • Sleep longer
  • Wake up at a more reasonable time
  • Feel well-rested and refreshed after sleeping

There is ongoing research to determine exactly how this medication influences sleep. One study found that 3 weeks of low-dose Doxepin treatment helped restore melatonin (another sleep-wake cycle regulator) to near-normal levels in insomnia patients.

In addition, sleep specialists believe that this medication may slow activity in the brain, helping us stay unconscious and get that much-needed sleep.



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